| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 265, Issue 3, 1443-1447, Jan, 1990
CL Williams and VA Lennon
Small cell carcinoma of the lung (SCC) expresses several characteristics of
neuronal cells, including voltage-gated Ca2+ channels (VGCC), and also
expresses muscarinic acetylcholine receptors (mAChR). In testing the
possibility that VGCC may be functionally coupled to mAChR in SCC cell
lines, we found that depolarization- dependent Ca2+ influx was inhibited by
carbachol (IC50 = 0.78 microM) and oxotremorine (IC50 = 0.69 microM).
Equilibrium dissociation constants for several mAChR antagonists indicated
that a mAChR of M3 subtype was involved. Exposure of SCC to carbachol
induced the hydrolysis of phosphoinositides and increased the cytosolic
free Ca2+ concentration ([Ca2+]i). The carbachol-mediated inhibition of
depolarization-dependent Ca2+ influx did not directly correlate with
increased [Ca2+]i but did correlate with inositol poly-phosphate
generation. The protein kinase C activators phorbol 12-myristate 13-
acetate or 1-oleoyl-2-acetyl-sn-glycerol neither mimicked nor amplified the
inhibitory effect of carbachol on Ca2+ influx. However, phorbol 12-
myristate 13-acetate suppressed the carbachol-induced inositol
polyphosphate generation and inhibition of depolarization-dependent Ca2+
influx. The inactive compound 4 alpha-phorbol had no effect. These data
suggest that the inhibition of VGCC caused by carbachol is not due to
protein kinase C activation, but rather is due to events mediated by
inositol polyphosphates. This is the first documentation of a role for
phosphoinositide hydrolysis in the functional coupling of mAChR and VGCC.
The expression of M3 mAChR functionally coupled to VGCC could have
therapeutic implications for SCC, in light of recent demonstrations that
cell proliferation can be influenced by activation of neurotransmitter
receptors.
Activation of M3 muscarinic acetylcholine receptors inhibits voltage- dependent calcium influx in small cell lung carcinoma
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Song, H. S. Sekhon, Y. Jia, J. A. Keller, J. K. Blusztajn, G. P. Mark, and E. R. Spindel Acetylcholine Is Synthesized by and Acts as an Autocrine Growth Factor for Small Cell Lung Carcinoma Cancer Res., January 1, 2003; 63(1): 214 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strassheim, S. H. Shafer, S. H. Phelps, and C. L. Williams Small Cell Lung Carcinoma Exhibits Greater Phospholipase C-{beta}1 Expression and Edelfosine Resistance Compared with Non-Small Cell Lung Carcinoma Cancer Res., May 1, 2000; 60(10): 2730 - 2736. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Sher, P. Cesare, A. Codignola, F. Clementi, P. Tarroni, A. Pollo, V. Magnelli, and E. Carbone Activation of delta -Opioid Receptors Inhibits Neuronal-Like Calcium Channels and Distal Steps of Ca2+-Dependent Secretion in Human Small-Cell Lung Carcinoma Cells J. Neurosci., June 1, 1996; 16(11): 3672 - 3684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Lennon, T. J. Kryzer, G. E. Griesmann, P. E. O'Suilleabhain, A. J. Windebank, A. Woppmann, G. P. Miljanich, and E. H. Lambert Calcium-Channel Antibodies in the Lambert-Eaton Syndrome and Other Paraneoplastic Syndromes N. Engl. J. Med., June 1, 1995; 332(22): 1467 - 1475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Strassheim and C. L. Williams P2Y2 Purinergic and M3 Muscarinic Acetylcholine Receptors Activate Different Phospholipase C-beta Isoforms That Are Uniquely Susceptible to Protein Kinase C-dependent Phosphorylation and Inactivation J. Biol. Chem., December 8, 2000; 275(50): 39767 - 39772. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
